Temporal regulation of lin-14 by the antagonistic action of two other heterochronic genes, lin-4 and lin-28.

Heterochronic genes form a regulatory pathway that controls the temporal sequence of the Caenorhabditis elegans postembryonic cell lineage. One of these genes, lin-14, encodes a nuclear protein that constitutes a temporal developmental switch. During wild-type development, lin-14 protein is abundant during early larval stage 1 (L1) to specific L1-specific cell lineages but is nearly undetectable at L2 and later stages to specify L2-specific and later cell lineages. To determine the roles played by other genes in executing this temporal switch, we have analyzed how lin-14 expression is regulated by other heterochronic genes. lin-4 is required to down-regulate lin-14 protein levels during the L1 stage, whereas lin-28 positively regulates lin-14 protein levels. The lin-4 gene product is a candidate for interacting with the negative regulatory element in the 3'-untranslated region of lin-14. lin-29 mutations do not affect lin-14 protein levels, consistent with lin-29 acting downstream of lin-14. Switching off lin-14 expression during the L1 stage is not triggered by the passage of time per se but, rather, is normally dependent on feeding or the feeding-dependent initiation of postembryonic cell division.